The invention relates generally to methods for producing dianhydrosugars and, more specifically, to an improved method for producing isosorbide from sorbitol at ambient pressures.
The production of anhydrosugars from sorbitol and similar sugar alcohols has been referenced in the patent literature for many years. The earliest work, in 1884, was done on 1,4:3,6-dianhydro-D-mannitol by Fauconnier. Interest has grown since then as a large body of chemical literature has developed in this area around production of isosorbide.
The 1,5:3,6-dianhydrohexitols, of which isosorbide is an example, are derived from natural products. Therefore, these compounds are classified as “renewable resources.” Furthermore, 1,4:3,6-dianhydrohexitols, such as isosorbide, can be used as starting materials and intermediates in chemical reactions. For example, isosorbide is reported to be useful in the production of pharmaceutical compounds, plastic and polymer production, and in other commercial uses such as in the production of polyurethane, polycarbonates, and polyesters.
Of the known isohexides, isosorbide is considered to be that of the highest importance. Acid catalysts are generally used for dehydrating the sugar alcohol starting material. Many catalysts and reaction conditions have been the subject of claims on improvements in its production. Examples of these are laid out below.
Several processes for the production of anhydrosugar alcohols (including isohexides such as isosorbide) are known. See, for example, U.S. Pat. No. 6,639,067 wherein a process is described for production of isosorbide that requires the use of an organic solvent. Alternatively U.S. Pat. No. 6,849,748 discloses a route to isosorbide that does not require an organic solvent but prefers a reaction run under reduced pressure to achieve good conversion of the starting sugar alcohol. PCT application number PCT/US99/00537 (WO 00/14081), discloses a continuous production method with recycling of organic solvent.
Various processes are known for producing anhydro-polyls starting from D-sorbitol (see e.g. B. R. Barker, J. Org. Chem., 35, 461 (1970), J. Feldmann et al., EP-OS 0 052 295 and DE-OS 30 14 626, Soltzberg et al., J. Am. Chem. Soc., 68, 919, 927, 930 (1946) and S. Ropuszinski et al., Prozed. Chem., 48, 665 (1969)). In all these processes water is generated in the presence of an acid catalyst and at a raised temperature. As the reaction progresses, the concentration of dianhydrosorbitol increases, while that of sorbitol decreases.
Most methods involve the use of concentrated acids and organic solvents. Goodwin et al. (Carbohydrate Res. 79 (1980), 133-141) have disclosed a method involving the use of acidic-cation-exchange resin in place of concentrated, corrosive acids, but with low yield of isosorbide product. However, a need continues in the art for a process for production of very pure isosorbide, at reasonable yields with inexpensive catalysts, and preferably without the use of potentially hazardous organic solvents or the use of expensive vacuum reactors.
Anhydro sugar alcohols are produced by dehydration of the corresponding sugar alcohols (or monoanhydro sugar alcohols) by the action of various dehydration catalysts, typically strong acid catalysts. Examples of these catalysts include sulfonated polystyrenes (H+ form) and various mineral acids of which sulfuric acid is the most popular.
In particular, a batch process for the formation of the dianhydro sugar alcohol isosorbide has been described as a two-step process involving intramolecular dehydration of sorbitol to sorbitan (1,4-monoanhydrosorbitol), and further reaction of sorbitan to isosorbide (1,4:3,6-dianhydrosorbitol) in an acid catalyzed dehydration-cyclization. In this process, an aqueous solution of sorbitol is charged to a batch reactor. The temperature is increased to 130° C.-135° C. under vacuum (35 mm Hg) to remove the water. When the sorbitol melt is free of water, a catalyst, usually sulfuric acid, is added and the temperature and vacuum levels are maintained. The operable temperature range of the reaction is very narrow. Higher temperatures lead to decomposition and charring of the end product, while lower temperatures inhibit the reaction rate due to difficulties in removal of the water of reaction. This reaction produces isosorbide and a higher molecular weight byproduct. The byproduct is presumably produced by water elimination between two or more sorbitol molecules, but its exact nature is not clearly defined. See G. Flche and M. Huchette, Starch/Starke (1986), 38(c), 26-30 and Roland Beck, Pharm. Mfg Inc. (1996), 97-100. Other monoanhydro byproducts, 2,5-anhydro-L-iditol and 2,5-anhydro-D-mannitol, are also known to be produced under some reaction conditions (Acta. Chem. Scand. B 35, 441-449 (1981)). The use of vacuum adds complexity and cost to the production of isosorbide.
For isosorbide to be used as a monomer in high volume polymers and copolymers, for applications such as containers, it needs to be produced in large quantities, preferably in a continuous process and with low operating costs.
WO 00/14081 describes a continuous process for producing anhydro sugar alcohols, especially isosorbide, comprising the steps of introducing at least one sugar alcohol or monoanhydro sugar alcohol into a reaction vessel; dehydrating the sugar alcohol or monoanhydro sugar alcohol in the presence of an acid catalyst and an organic solvent to form a reaction product which is at least partly soluble in the organic solvent; removing water from the reaction vessel; removing organic solvent comprising the dissolved reaction product from the reaction vessel; separating the reaction product from the removed organic solvent; and recycling the organic solvent into the reaction vessel. The large amounts of organic solvent required for such a process make it economically and environmentally undesirable.
U.S. Pat. No. 6,407,266 describes a continuous process in which a process stream containing at least one sugar alcohol or monoanhydro sugar alcohol and, optionally, water is introduced to the first stage of a multistage reactor and then intimately contacted with a countercurrent flow of an inert gas at elevated temperature. This inert gas removes the bulk of any water present in the process stream. This dewatered process stream is then intimately contacted with a dehydration catalyst, with a counter current flow of an inert gas at elevated temperatures to remove water of reaction as formed. Finally, the product is removed from the bottom of the reactor.
The reaction product obtained by processes such as the above, contains about 70 to 80% by weight isosorbide and 20 to 30% undesired reaction byproducts. The reaction product thus needs to be subjected to one or more separation steps, such as evaporation, distillation or chromatographic separation, to isolate the isosorbide. Chromatographic separation is disclosed in U.S. Patent Application No. 60/246,038 (filed 6 Nov. 2000). Separation by vaporization or distillation is difficult because of the low vapor pressure of isosorbide. For example, it has been found that at 140° C., the vapor pressure is only 1.75 mm Hg. Evaporation or distillation at temperatures not much higher than about 140° C. is desirable to minimize product degradation and obtain good purity isosorbide, but the recovery is poor. At higher temperatures, e.g., 170° C., more isosorbide is recovered, but it is of poorer quality.
U.S. Pat. No. 4,564,692 discloses a process using crystallization from aqueous solutions to obtain the high purity needed for applications as polyol components in polyester and polyurethane polymers.
Many of the previous inventions claim the use of a high vacuum to achieve a high degree of water removal to drive the reaction which progresses by the loss of water. A need exists for a continuous process that provides isosorbide in high selectivity at high sorbitol conversion without the high costs associated with running the reaction under high vacuum or the use of organic solvents in the process which increase the operating costs and increase the difficulty of obtaining environmental permits.
In the condensation reaction of sorbitol to 1,4-sorbitan followed by a subsequent condensation reaction to form isosorbide, earlier researchers have proscribed the removal of water to drive the reaction. Most prior art references recommend the use of vacuum to facilitate water removal. The standard preparation of isosorbide has been described in the literature as involving the treatment of sorbitol with sulfuric acid (Hockett, R. C., Fletcher, Jr., J. G., Sheffield, E. L., Goepp, Jr., R. M., Soltzberg, S. J. Am. Chem. So. 1946, 68, 930). The reaction is carried out under vacuum and at elevated temperatures. In the reaction, sorbitol is first converted to either 1,4-soribitan or 3,6-sorbitan, which results in the production of an equivalent of water. The sorbitan is next converted to isosorbide, which again produces an equivalent of water. The water is well known to inhibit the reaction; small amounts of water dramatically impact the reaction rate. The purpose of the vacuum was to remove the water formed during the reaction. Subsequent methods have used a reverse flow of a gas, such as nitrogen, to remove water from the reaction mixture. The need for operating under a vacuum or using a gas stream to remove water adds to the complexity of reactor design as well as operating costs. Surprisingly, we have found that high selectivity and good reaction rates can be achieved at temperatures of around 150° C. and that no vacuum or sparging gas for water removal is required.